The 1998 NIH Symposium, " Gender and Pain ", organized by Ruda, brought together researchers from all over the country to discuss male/female differences in the epidemiology, physiology, pharmacology, and psychology of pain. Ladarola, working with such collaborators as Dr. H-Y. T. Yang, Jun Gu, and Donna Messersmith, has worked on describing the multi-step genetic expression of the precursor proteins for dynorphin and enkephalin under painful and stressful stimuli. His lab has helped to develop the new methods required for these experiments, including transient transfection (infection of a cell with nucleic acid to induce replication) and injections of drugs such as cocaine, morphine, and clonidine. Most recently, he and his co-workers have employed subtraction cloning to identify new pain-relevant genes in the dorsal horn.

In the mid-1990s, Iadarola, with Gracely, Dionne, and colleague Robert Coghill, began a series of studies of the brain, using PET [Positron Emission Tomography] imaging. In these images, researchers are for the first time able to observe the activity of brain cells responding to, and integrating, the pain information sent by the nervous system. They can compare the differential responses of normal volunteers and pain patients to heat, cold, and inflammation, and can correlate these with the subject's verbal assessment of the pain sensation.

A particularly exciting project began in 1998, when Iadarola and his co-workers decided to investigate a genetic therapy for chronic pain. They developed an innovative gene-transfer model that triggers meningeal cells to secrete beta-endorphin into the cerebrospinal fluid. The new therapy will soon be tested in clinical trials. For more information please view the NIH Catalyst article and NIH Catalyst commentary.

Hyperalgesic responses to heat stimuli in estrous female rats v. non-estrous female and male rats. From Heather Bradshaw, Julie Miller, Qingdong Ling, Kirsten Malsnee, and M.A. Ruda, Sex differences and phases of the estrous cycle alter the response of spinal cord dynorphin neurons to peripheral inflammation and hyperalgesia. Pain v. 88 (2000): 97.